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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no deviations from standard test guidelines and no methodological deficiences, which do not affect the quality of teh relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Supplier: ATOCHEM
Batch number: 1-220-1
Description: colorless liquid
Assay: > 98.5 %w
Acidity: < 10 mg/kg
Container: glass flask
Storage conditions: at room temperature and protected from light

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
On the day of treatment, the animals were 2 to 4 months old and had a mean body weight ± standard devition of 2.8 ± 0.4 kg.
Acclimatation: at least 5 days before the beginning of the study.
Identification : individual ear tag.

The conditions in the animal room were set as follows:
- temperature: 18±3°C
- relative humidity: 30 to 70%
- light/dark cycle: 12h/12h
The temperature and relative humidity were under continuous control and recording. In addition to these daily checks, the housing conditions and corresponding instrumentation and equipment were verified and calibrated at regular intervals.

The animals were housed individually in polystyrene cages (35 x 55 x 32 cm).
Each cage was equiped with a food container and a water bottle.

All the animals had free access to 110 C pelleted diet.
Food is analysed regularly by the supplier for composition and contaminant levels.

Drinking water filtered by a FG Millipore membrane (0.22 µm) was provided ad libitum.
Bacteriological and chemical analyses of water are performed regularly by external laboratories. These analyses include the detection of possible contaminants (pesticides, heavy metals and nitroamines).
No contaminants were known to have been present in the diet, drinking water or bedding material at levels which may be expected to have interfered with or prejudiced the outcome of the study.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: The left flank of each animal served as control
Amount / concentration applied:
Doses of 0.5 ml of the test item were placed on a 6 cm2 dry hydrophilic gauze pad, which then applied to the right flank of the animals.
Duration of treatment / exposure:
In first instance, duration of exposure was 4 hours on one flank on a single animal.

Since the test item was no irritant on the first animal, it was then applied for 4 hours to two other animals.
Observation period:
The skin was examined approximately 1 hour, 24, 48 and 72 hours after removal of the dressing.
SInce there was persistent irritation reactions at 72 hours, the observation period was extended to a maximum of 14 days (until day 15) in order to determine the progess of the lesions and their irreversibility.
Any change in the animals' behaviour was noted.
Number of animals:
One in fist instance and 2 for the second run.
Details on study design:
The day before treatment, both flanks of each animal were clipped using electric clippers and the skin of each animal was examined in order to check the absence of any signs of skin irritation.

The test item and the gauze pad were held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

The untreated skin served as control.

Subsequently, the dressings were removed and no residual test substance was oberved.

The animals were then replaced into their individual cages.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 h
Score:
2.7
Max. score:
4
Reversibility:
not fully reversible within: 8 days
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 h
Score:
3
Max. score:
4
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 h
Score:
2.7
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 h
Score:
1.3
Max. score:
4
Reversibility:
not fully reversible within: 6 days
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 h
Score:
2
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 h
Score:
3
Max. score:
4
Other effects:
From day 4, a dryness of the skin was observed at the treatment site for all 3 animals.
On day 15, a dryness of the skin persisted in 2 animals.
No ulceration or necrosis were noted.

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
As the mean scores for erythema, oedema for 2 out of 3 animals reached the criteria values for irritation, under our experimental conditions, n-Pentyl bromide was considered as irritant when administered by cutaneous route in rabbits.
Executive summary:

The skin irritation potential of the test material was determined according to the OECD 404 guidelines. Three rabbits were exposed to 0.5 ml of the test material for 4 hours, the site was them observed at intervals over a period of 15 days.

The mean scores over 24, 48 and 72 hours for indivudual animals were 3.7, 1.7 and 2.7 for erythema and 2.7, 0 and 2.7 for oedema.

Erytheam and oedema were reversible. From day 4, a dryness of the skin was observed at the treatment site.

The test material was determined to be irritating.

UnderRegulation 1272/2008 the test material should be classed as "Skin Irrit. 2" and assigned the hazard phrase "H315: Causes Irritation to the Skin" and signal word "Warning".